Critically ill patients who require treatment with mechanical ventilation (MV) are at an increased risk for complications that lead to prolonged days on the ventilator, high mortality, and increased resource use. Ventilation is delivered through an artificial airway, usually an endotracheal tube (ETT). Although essential, the ETT increases the risk of micro aspiration of secretions from the mouth and oropharynx into the lungs. Secretions may contain bacteria from the oral cavity, or gastric contents secondary to reflux. Therefore, micro aspiration can lead to ventilator-associated conditions (VAC), including lung injury and pneumonia. Several interventions, termed a ventilator bundle, have been identified as best practices for MV patients and are routinely implemented. These targeted interventions have reduced infection, but do not address all factors associated with the development of VAC. Micro aspiration of secretions still occurs, increasing the risk for harm. Micro aspiration starts with accumulation of secretions in the mouth and oropharynx. Removal of oral secretions is not part of any ventilator bundle, and the procedure is neither standardized nor based on evidence. Therefore, a nursing intervention, enhanced oropharyngeal suctioning, that focuses on regular removal of these secretions beyond existing practices is important. This study will assess outcomes of a Nursing Oral Suction Protocol Intervention to Reduce Aspiration and Ventilator-Events (NO-ASPIRATE), a standardized, enhanced oropharyngeal suction procedure delivered every 4 hours. The long-term goal is to improve the care of patients on MV who are at a high risk for complications that begin with micro aspiration of secretions. The primary aim of this study is to assess if the addition of the NO-ASPIRATE intervention will be more effective than usual care in preventing micro aspiration in intubated, MV patients. A randomized, single- blind trial design-enrolling a convenience sample (n=560) of critically-ill, ventilated patients, age 18 years or older, who have an oral ETT-will be conducted at a tertiary care hospital to achieve a target sample size of 400 subjects randomized to receive either the NO-ASPIRATE (experimental group) or a usual care/sham intervention (usual care group) delivered every 4 hours by a study team member. Tracheal and oral specimens for analysis of -amylase as a biomarker for micro aspiration will be obtained twice per day. VAC will be assessed by an algorithm developed by the Centers for Disease Control and Prevention. All subjects will receive the standard of care for MV patients. Data analysis will include logistic regression, survival analysis, and generalized estimating equations. The study will provide data to develop evidence-based standards for oral suction, a nurse-driven intervention, to prevent micro aspiration in critically ill patients.